0000000001303519
AUTHOR
Sami Kortet
showing 10 related works from this author
Structure-Activity Relationship Analysis of 3-Phenylcoumarin-Based Monoamine Oxidase B Inhibitors
2018
Monoamine oxidase B (MAO-B) catalyzes deamination of monoamines such as neurotransmitters dopamine and norepinephrine. Accordingly, small-molecule MAO-B inhibitors potentially alleviate the symptoms of dopamine-linked neuropathologies such as depression or Parkinson's disease. Coumarin with a functionalized 3-phenyl ring system is a promising scaffold for building potent MAO-B inhibitors. Here, a vast set of 3-phenylcoumarin derivatives was designed using virtual combinatorial chemistry or rationally de novo and synthesized using microwave chemistry. The derivatives inhibited the MAO-B at 100 nM−1 μM. The IC50 value of the most potent derivative 1 was 56 nM. A docking-based structure-activi…
Blocking oestradiol synthesis pathways with potent and selective coumarin derivatives
2018
A comprehensive set of 3-phenylcoumarin analogues with polar substituents was synthesised for blocking oestradiol synthesis by 17-b-hydroxysteroid dehydrogenase 1 (HSD1) in the latter part of the sulphatase pathway. Five analogues produced 62% HSD1 inhibition at 5 mM and, furthermore, three of them produced 68% inhibition at 1 mM. A docking-based structure-activity relationship analysis was done to determine the molecular basis of the inhibition and the cross-reactivity of the analogues was tested against oestrogen receptor, aromatase, cytochrome P450 1A2, and monoamine oxidases. Most of the analogues are only modestly active with 17-b-hydroxysteroid dehydrogenase 2 – a requirement for lowe…
Enzymatic Resolution of 3-oxodicyclopentadiene on a Decagram Scale
2018
The chiral building block 3-oxodicyclopentadiene (1) can be readily resolved on a decagram scale by a short sequence consisting of (1) reduction to the corresponding endo-alcohol, (2) enzymatic oxidative resolution with a ketoreductase enzyme to give (+)-1 and the (+)-form of the endo-alcohol, and (3) reoxidation of the (+)-endo-alcohol with another ketoreductase to give (–)-1. With a selectivity factor of 310, the enantiomeric ratios of the resolved (+)-endo-alcohol and (+)-ketone are both >99:1. Both enzymatic oxidations could be performed with a at least 300:1 substrate/catalyst ratio (w/w).
Molecular docking-based design and development of a highly selective probe substrate for UDP-glucuronosyltransferase 1A10
2018
Intestinal and hepatic glucuronidation by the UDP-glucuronosyltransferases (UGTs) greatly affect the bioavailability of phenolic compounds. UGT1A10 catalyzes glucuronidation reactions in the intestine, but not in the liver. Here, our aim was to develop selective, fluorescent substrates to easily elucidate UGT1A10 function. To this end, homology models were constructed and used to design new substrates, and subsequently, six novel C3-substituted (4-fluorophenyl, 4-hydroxyphenyl, 4-methoxyphenyl, 4-(dimethylamino)phenyl, 4-methylphenyl, or triazole) 7-hydroxycoumarin derivatives were synthesized from inexpensive starting materials. All tested compounds could be glucuronidated to nonfluorescen…
Catalytic Enantioselective Total Synthesis of (+)-Lycoperdic Acid.
2020
A concise enantio- and stereocontrolled synthesis of (+)-lycoperdic acid is presented. The stereochemical control is based on iminium-catalyzed Mukaiyama–Michael reaction and enamine-catalyzed organocatalytic α-chlorination steps. The amino group was introduced by azide displacement, affording the final stereochemistry of (+)-lycoperdic acid. Penultimate hydrogenation and hydrolysis afforded pure (+)-lycoperdic acid in seven steps from a known silyloxyfuran. peerReviewed
CCDC 1827648: Experimental Crystal Structure Determination
2018
Related Article: Katja Kärki, Juha H. Siitonen, Mona Cederström, Sami Kortet, Petri M. Pihko|2018|Synlett|29|1723|doi:10.1055/s-0037-1610109
CCDC 1831369: Experimental Crystal Structure Determination
2018
Related Article: Katja Kärki, Juha H. Siitonen, Mona Cederström, Sami Kortet, Petri M. Pihko|2018|Synlett|29|1723|doi:10.1055/s-0037-1610109
CCDC 1972521: Experimental Crystal Structure Determination
2020
Related Article: Sami Kortet, Aurélie Claraz, Petri M. Pihko|2020|Org.Lett.|22|3010|doi:10.1021/acs.orglett.0c00772
CCDC 1827649: Experimental Crystal Structure Determination
2018
Related Article: Katja Kärki, Juha H. Siitonen, Mona Cederström, Sami Kortet, Petri M. Pihko|2018|Synlett|29|1723|doi:10.1055/s-0037-1610109
CCDC 1827647: Experimental Crystal Structure Determination
2018
Related Article: Katja Kärki, Juha H. Siitonen, Mona Cederström, Sami Kortet, Petri M. Pihko|2018|Synlett|29|1723|doi:10.1055/s-0037-1610109